Constructing Control Samples For The Australian And Other Populations: Improving Power And False Positive Rates In The Next Generation Of Genetic Association Studies With A Focus On Controlling For Fine-scale Population Structure In DNA Sequence Data
Funder
National Health and Medical Research Council
Funding Amount
$283,447.00
Summary
Individuals who live near each other tend to be more similar genetically than individuals who live in different parts of the world. One reason is that they share more of their genetic ancestry. There can be very subtle differences in patterns of genetic variation even within countries. Accounting for these subtle differences can be important for studies of the genetic basis of diseases. We will develop novel statistical methods to control for these genetic differences in disease studies.
Identifying Novel Gene Mutations For Molecular Diagnosis Of Familial Hemiplegic Migraine
Funder
National Health and Medical Research Council
Funding Amount
$623,460.00
Summary
This proposal aims to identify novel FHM genes by undertaking an NGS screen of the whole exome of 209 FHM patient samples. We will test the pathological relevance of detected novel mutations by functional analysis in human cell models and using patient-specific stem cell techniques. Using whole genome NGS technology to identify novel mutations will assist in the design and development of a comprehensive NGS approach to diagnose and differentiate this severe neurological disorder.
Biobank Networks, Medical Research And The Challenge Of Globalisation
Funder
National Health and Medical Research Council
Funding Amount
$790,698.00
Summary
Medical research increasingly relies on large-scale biobanks that store tissue samples from healthy donors or patients. Over the past decade, international networks of biobanks have been established. These are scientifically valuable but raise numerous legal and ethical challenges. In this project we will generate evidence to inform the development of ethically rigorous strategies to ensure that Australian donors and biobanks contribute to, and benefit from, international biobank networks.
In the study of common disease, it is becoming apparent that it is not only an individual's DNA sequence that can encode susceptibility to disease, but also chemical modifications to that sequence. Despite the importance of these chemical modifications in the development of disease, there has been no comprehensive survey of the extent which they are transmitted across generations in humans. This proposal will investigate how one of those modifications, DNA methylation, is inherited.
Immunoglobulin Germline Genes, BCR Repertoire Development And Disease Susceptibility. An Investigation Of Haplotypic Variation Between Individuals
Funder
National Health and Medical Research Council
Funding Amount
$519,828.00
Summary
The immune system is capable of making a repertoire of protective antibodies including literally tens of millions of different specificities. These are produced by permutations and combinations of a small set of ‘germline’ genes. This project will analyse how individual variations in the germline genes lead to individual differences in the repertoires of available antibodies, and will investigate whether or not such differences contribute to our susceptibility to infection and autoimmune disease ....The immune system is capable of making a repertoire of protective antibodies including literally tens of millions of different specificities. These are produced by permutations and combinations of a small set of ‘germline’ genes. This project will analyse how individual variations in the germline genes lead to individual differences in the repertoires of available antibodies, and will investigate whether or not such differences contribute to our susceptibility to infection and autoimmune diseases.Read moreRead less
Population Based Genetic Testing For High-risk Breast And Ovarian Cancer Predisposition Genes
Funder
National Health and Medical Research Council
Funding Amount
$1,112,985.00
Summary
Inherited mutations in BRCA1 and BRCA2 confer a very high risk of breast and ovarian cancer. Importantly, once carriers are identified, effective strategies are available that can dramatically reduce the risk of cancer. We will perform genetic testing of a healthy western population to identify breast/ovarian cancer genes before the women develop cancer. Population-based screening could significantly reduce the incidence of these diseases.
Novel Fragile X Syndrome Prevalence Estimates In 100,000 Australian Newborns, Prognostic And Health-economic Outcomes: A Retrospective Newborn Screening Study
Funder
National Health and Medical Research Council
Funding Amount
$769,866.00
Summary
Fragile X syndrome (FXS) is a common heritable cause of intellectual disability and co-morbid autism, caused by epigenetic silencing of the FMR1 gene. This will be the world’s largest FXS mutation prevalence study conducted in 100,000 newborns using a novel test targeting epigenetic changes, and will also explore the prognostic outcomes, costs and benefits associated with FXS newborn screening, providing conclusions regarding expanding the current newborn screening in Australia to include FXS.
Osteoporosis is the commonest metabolic bone disease worldwide, and costs Australia >1% of GDP. It is a strongly inherited disease. We recently completed a genome-wide association study in 2000 postmenopausal women with either very high or very low bone density, and identified many genes contributing to BMD. The current study aims to use next-generation sequencing to study these women in greater genetic depth, aiming to identify more clearly the exact genetic determinants of bone mass.
Population Genomics Of Plasmodium Vivax In Papua New Guinea
Funder
National Health and Medical Research Council
Funding Amount
$597,238.00
Summary
Plasmodium vivax malaria is a serious global public health problem that has not received the attention it deserves, despite having serious clinical implications and presenting a major problem for regional malaria control programmes. In a study of people living in a malarious area of PNG, we aim to investigate the diversity of natural parasite populations, to better understand the possible effects of malaria control interventions on transmission and human immunity.
Mapping Plasmodium Falciparum Population Structure And The Source Of Outbreaks In Papua New Guinea
Funder
National Health and Medical Research Council
Funding Amount
$534,786.00
Summary
Molecular studies to map malaria parasite populations are essential for planning and maintaining malaria control in at risk areas. We will develop molecular tools to map malaria parasite populations in Papua New Guinea at high resolution. We will then investigate whether these tools can be used to pinpoint the source of infections in regions where malaria is normally absent. The project will provide valuable information to help focus malaria control efforts to areas where they will be most effec ....Molecular studies to map malaria parasite populations are essential for planning and maintaining malaria control in at risk areas. We will develop molecular tools to map malaria parasite populations in Papua New Guinea at high resolution. We will then investigate whether these tools can be used to pinpoint the source of infections in regions where malaria is normally absent. The project will provide valuable information to help focus malaria control efforts to areas where they will be most effective.Read moreRead less